From Necklace Quivers to the F-theorem, Operator Counting, and T(U(N))

The matrix model of Kapustin, Willett, and Yaakov is a powerful tool for exploring the properties of strongly interacting superconformal Chern-Simons theories in 2+1 dimensions. In this paper, we use this matrix model to study necklace quiver gauge theories with {\cal N}=3 supersymmetry and U(N)^d gauge groups in the limit of large N. In its simplest application, the matrix model computes the free energy of the gauge theory on S^3. The conjectured F-theorem states that this quantity should decrease under renormalization group flow. We show that for a simple class of such flows, the F-theorem holds for our necklace theories. We also provide a relationship between matrix model eigenvalue distributions and numbers of chiral operators that we conjecture holds more generally. Through the AdS/CFT correspondence, there is therefore a natural dual geometric interpretation of the matrix model saddle point in terms of volumes of 7-d tri-Sasaki Einstein spaces and some of their 5-d submanifolds. As a final bonus, our analysis gives us the partition function of the T(U(N)) theory on S^3.Comment: 3 figures, 41 pages; v2 minor improvements, refs adde

Quantitative Mass Spectrometry Analysis Reveals Similar Substrate Consensus Motif for Human Mps1 Kinase and Plk1

Background Members of the Mps1 kinase family play an essential and evolutionarily conserved role in the spindle assembly checkpoint (SAC), a surveillance mechanism that ensures accurate chromosome segregation during mitosis. Human Mps1 (hMps1) is highly phosphorylated during mitosis and many phosphorylation sites have been identified. However, the upstream kinases responsible for these phosphorylations are not presently known. Methodology/Principal Findings Here, we identify 29 in vivo phosphorylation sites in hMps1. While in vivo analyses indicate that Aurora B and hMps1 activity are required for mitotic hyper-phosphorylation of hMps1, in vitro kinase assays show that Cdk1, MAPK, Plk1 and hMps1 itself can directly phosphorylate hMps1. Although Aurora B poorly phosphorylates hMps1 in vitro, it positively regulates the localization of Mps1 to kinetochores in vivo. Most importantly, quantitative mass spectrometry analysis demonstrates that at least 12 sites within hMps1 can be attributed to autophosphorylation. Remarkably, these hMps1 autophosphorylation sites closely resemble the consensus motif of Plk1, demonstrating that these two mitotic kinases share a similar substrate consensus. Conclusions/Significance hMps1 kinase is regulated by Aurora B kinase and its autophosphorylation. Analysis on hMps1 autophosphorylation sites demonstrates that hMps1 has a substrate preference similar to Plk1 kinase

Network Homophily and the Evolution of the Pay-It-Forward Reciprocity

The pay-it-forward reciprocity is a type of cooperative behavior that people who have benefited from others return favors to third parties other than the benefactors, thus pushing forward a cascade of kindness. The phenomenon of the pay-it-forward reciprocity is ubiquitous, yet how it evolves to be part of human sociality has not been fully understood. We develop an evolutionary dynamics model to investigate how network homophily influences the evolution of the pay-it-forward reciprocity. Manipulating the extent to which actors carrying the same behavioral trait are linked in networks, the computer simulation model shows that strong network homophily helps consolidate the adaptive advantage of cooperation, yet introducing some heterophily to the formation of network helps advance cooperation's scale further. Our model enriches the literature of inclusive fitness theory by demonstrating the conditions under which cooperation or reciprocity can be selected for in evolution when social interaction is not confined exclusively to relatives

Loss of Cytoplasmic CDK1 Predicts Poor Survival in Human Lung Cancer and Confers Chemotherapeutic Resistance

The dismal lethality of lung cancer is due to late stage at diagnosis and inherent therapeutic resistance. The incorporation of targeted therapies has modestly improved clinical outcomes, but the identification of new targets could further improve clinical outcomes by guiding stratification of poor-risk early stage patients and individualizing therapeutic choices. We hypothesized that a sequential, combined microarray approach would be valuable to identify and validate new targets in lung cancer. We profiled gene expression signatures during lung epithelial cell immortalization and transformation, and showed that genes involved in mitosis were progressively enhanced in carcinogenesis. 28 genes were validated by immunoblotting and 4 genes were further evaluated in non-small cell lung cancer tissue microarrays. Although CDK1 was highly expressed in tumor tissues, its loss from the cytoplasm unexpectedly predicted poor survival and conferred resistance to chemotherapy in multiple cell lines, especially microtubule-directed agents. An analysis of expression of CDK1 and CDK1-associated genes in the NCI60 cell line database confirmed the broad association of these genes with chemotherapeutic responsiveness. These results have implications for personalizing lung cancer therapy and highlight the potential of combined approaches for biomarker discovery

Lutzomyia Sand Fly Diversity and Rates of Infection by Wolbachia and an Exotic Leishmania Species on Barro Colorado Island, Panama

Certain sand fly species living inside or on the edge of tropical forests are well known to transmit a protozoan to humans, which in lowland Panama develops into a cutaneous form of leishmaniasis; open, itching sores on the face and extremities requiring aggressive treatment with antimonial compounds. Morphological characters and DNA sequence from mitochondrial and nuclear gene fragments permitted us to identify and then establish historical relationships among 20 common sand fly species occurring in the understory of Barro Colorado Island, a forested preserve in the middle of the Panama Canal. Individuals in three of these sand fly species were found to be 26–43% infected by Leishmania naiffi, a species hitherto known only from the Amazonian region and the Caribbean. We then screened the same 20 sand fly species for the cytoplasmically transmitted bacteria Wolbachia pipientis, finding three infected at high rates, each by a distinct strain. Lutzomyia trapidoi, the most likely transmitter of Leishmania to humans in Panama, was among the Wolbachia-infected species, thus marking it as a possible high-value target for future biocontrol studies using the bacteria either to induce mating incompatabilities or to drive selected genes into the population

Incomplete information about the partner affects the development of collaborative strategies in joint action.

Physical interaction with a partner plays an essential role in our life experience and is the basis of many daily activities. When two physically coupled humans have different and partly conflicting goals, they face the challenge of negotiating some type of collaboration. This requires that both participants understand their partner's state and current actions. But, how would the collaboration be affected if information about their partner were unreliable or incomplete? We designed an experiment in which two players (a dyad) are mechanically connected through a virtual spring, but cannot see each other. They were instructed to perform reaching movements with the same start and end position, but through different via-points. In different groups of dyads we varied the amount of information provided to each player about his/her partner: haptic only (the interaction force perceived through the virtual spring), visuo-haptic (the interaction force is also displayed on the screen), and partner visible (in addition to interaction force, partner position is continuously displayed on the screen). We found that incomplete information about the partner affects not only the speed at which collaboration is achieved (less information, slower learning), but also the actual collaboration strategy. In particular, incomplete or unreliable information leads to an interaction strategy characterized by alternating leader-follower roles. Conversely, more reliable information leads to more synchronous behaviors, in which no specific roles can be identified. Simulations based on a combination of game theory and Bayesian estimation suggested that synchronous behaviors correspond to optimal interaction (Nash equilibrium). Roles emerge as sub-optimal forms of interaction, which minimize the need to account for the partner. These findings suggest that collaborative strategies in joint action are shaped by the trade-off between the task requirements and the uncertainty of the information available about the partner

Phylogeography of Supralittoral Rocky Intertidal Ligia Isopods in the Pacific Region from Central California to Central Mexico

Ligia isopods are widely distributed in the Pacific rocky intertidal shores from central California to central Mexico, including the Gulf of California. Yet, their biological characteristics restrict them to complete their life cycles in a very narrow range of the rocky intertidal supralittoral. Herein, we examine phylogeographic patterns of Ligia isopods from 122 localities between central California and central Mexico. We expect to find high levels of allopatric diversity. In addition, we expect the phylogeographic patterns to show signatures of past vicariant events that occurred in this geologically dynamic region.We sequenced two mitochondrial genes (Cytochrome Oxidase I and 16S ribosomal DNA). We conducted Maximum Likelihood and Bayesian phylogenetic analyses. We found many divergent clades that, in general, group according to geography. Some of the most striking features of the Ligia phylogeographic pattern include: (1) deep mid-peninsular phylogeographic breaks on the Pacific and Gulf sides of Baja peninsula; (2) within the Gulf lineages, the northern peninsula is most closely related to the northern mainland, while the southern peninsula is most closely related to the central-southern mainland; and, (3) the southernmost portion of the peninsula (Cape Region) is most closely related to the southernmost portion of mainland.Our results shed light on the phylogenetic relationships of Ligia populations in the study area. This study probably represents the finest-scale phylogeographic examination for any organism to date in this region. Presence of highly divergent lineages suggests multiple Ligia species exist in this region. The phylogeographic patterns of Ligia in the Gulf of California and Baja peninsula are incongruent with a widely accepted vicariant scenario among phylogeographers, but consistent with aspects of alternative geological hypotheses and phylo- and biogeographic patterns of several other taxa. Our findings contribute to the ongoing debate regarding the geological origin of this important biogeographic region

Stem cell‐derived enteroid cultures as a tool for dissecting host‐parasite interactions in the small intestinal epithelium.

Toxoplasma gondii and Cryptosporidium spp. can cause devastating pathological effects in humans and livestock, and in particular to young or immunocompromised individuals. The current treatment plans for these enteric parasites are limited due to long drug courses, severe side effects, or simply a lack of efficacy. The study of the early interactions between the parasites and the site of infection in the small intestinal epithelium has been thwarted by the lack of accessible, physiologically relevant, and species-specific models. Increasingly, 3D stem cell-derived enteroid models are being refined and developed into sophisticated models of infectious disease. In this review we shall illustrate the use of enteroids to spearhead research into enteric parasitic infections, bridging the gap between cell line cultures and in vivo experiments

Quantifying the Effects of Elastic Collisions and Non-Covalent Binding on Glutamate Receptor Trafficking in the Post-Synaptic Density

One mechanism of information storage in neurons is believed to be determined by the strength of synaptic contacts. The strength of an excitatory synapse is partially due to the concentration of a particular type of ionotropic glutamate receptor (AMPAR) in the post-synaptic density (PSD). AMPAR concentration in the PSD has to be plastic, to allow the storage of new memories; but it also has to be stable to preserve important information. Although much is known about the molecular identity of synapses, the biophysical mechanisms by which AMPAR can enter, leave and remain in the synapse are unclear. We used Monte Carlo simulations to determine the influence of PSD structure and activity in maintaining homeostatic concentrations of AMPARs in the synapse. We found that, the high concentration and excluded volume caused by PSD molecules result in molecular crowding. Diffusion of AMPAR in the PSD under such conditions is anomalous. Anomalous diffusion of AMPAR results in retention of these receptors inside the PSD for periods ranging from minutes to several hours in the absence of strong binding of receptors to PSD molecules. Trapping of receptors in the PSD by crowding effects was very sensitive to the concentration of PSD molecules, showing a switch-like behavior for retention of receptors. Non-covalent binding of AMPAR to anchored PSD molecules allowed the synapse to become well-mixed, resulting in normal diffusion of AMPAR. Binding also allowed the exchange of receptors in and out of the PSD. We propose that molecular crowding is an important biophysical mechanism to maintain homeostatic synaptic concentrations of AMPARs in the PSD without the need of energetically expensive biochemical reactions. In this context, binding of AMPAR with PSD molecules could collaborate with crowding to maintain synaptic homeostasis but could also allow synaptic plasticity by increasing the exchange of these receptors with the surrounding extra-synaptic membrane